Shionogi files for approval of oral COVID-19 antiviral in Japan, brushing off missed clinical endpoint in race to market

Shionogi is about to find out what it takes to get a COVID-19 antiviral to market in Japan. Having missed the primary clinical endpoint in a phase 2b, Shionogi has filed for approval on the strength of evidence its oral antiviral S-217622 reduces viral load and certain symptoms.

The phase 2b randomized 428 patients with mild to moderate COVID-19 to receive S-217622 or placebo once a day for five days. At the end of the treatment period, Shionogi saw no significant difference in the time-weighted average change in the total score of 12 COVID-19 symptoms, causing the study to miss its primary clinical endpoint. Shionogi did track significant improvements in respiratory symptoms. 

Pfizer’s leading oral COVID-19 drug Paxlovid also missed a primary endpoint of self-reported, sustained alleviation of all symptoms for four consecutive days in a study of unvaccinated, low-risk and vaccinated, higher-risk patients, but it was shown to reduce hospitalization and death in that trial and in another study.

Shionogi is yet to share phase 2b data on the effect of S-217622 on hospitalization and death, leaving the viral titer endpoint as the strongest evidence that the drug works. By Day 4, Shionogi saw significant reductions in viral titer, one of the primary endpoints, and the “proportion of subjects with positive viral titer, which was below 10% in the S-217622 treated arms.” 

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In an earlier phase 2a, Shionogi linked S-217622 to a median two-day reduction in time to the negative SARS-CoV-2 viral titer and found that on Day 4, “the proportion of subjects with positive viral titer decreased by approximately 60-80%, compared to the placebo group.” 

Shionogi will gather more evidence of the efficacy of S-217622 in ongoing late-phase studies that are testing the antiviral in more than 1,000 patients with mild to moderate COVID-19 symptoms and 300 to 600 people who are either asymptomatic or only have mild symptoms. But with omicron recently putting pressure on supplies of existing treatments, Shionogi isn’t waiting on the data to file for approval.

The Osaka, Japan-based drugmaker has filed for conditional approval in Japan. If approved, S-217622 will join Merck’s Lagevrio and Pfizer’s Paxlovid on the list of oral COVID-19 antivirals available in Japan. S-217622, like Paxlovid, is a 3CL protease inhibitor.